Tivozanib ( Fotivda ) is a potent and highly selective VEGFR inhibitor. TIVO-3 is a phase 3 study designed to compare the efficacy and safety of Tivozanib with those of Sorafenib ( Nexavar ) as 3rd and 4th line therapy in patients with metastatic renal cell carcinoma ( RCC ).
Subjects with renal cell carcinoma who failed 2 or 3 prior systemic regimens, one of which included a VEGFR tyrosine kinase inhibitor ( VEGFR TKI ) other than Sorafenib or Tivozanib, were stratified by IMDC risk category and type of prior therapy ( two TKIs; TKI plus checkpoint inhibitor ( CPI ); TKI plus other ) then randomized in a 1:1 ratio to Tivozanib or Sorafenib.
The 2 arms were well balanced for demographics and prior cancer history. 60% of subjects had 2 prior lines of therapy and 40% had 3 prior lines. 26% had prior treatment with a CPI.
Patients treated with Tivozanib demonstrated progression-free survival ( PFS ) superiority compared to Sorafenib, 5.6 ( 95% CI 7.3 - 5.3 ) versus 3.9 months ( 95% CI 5.6 – 3.7; hazard ratio, HR 0.73; p=0.02 ).
The objective response rate ( ORR ) was 18% for Tivozanib compared to 8% for Sorafenib ( p=0.02 ).
44% of Tivozanib treated subjects experienced a grade 3 treatment-related adverse event compared to 55% for Sorafenib.
The predefined, interim analysis for overall survival ( OS ) performed two years after enrollment was closed had a hazard ratio of 0.99 based on 227 events.
The final analysis will be presented based on an estimate of 263 events.
In conclusion, Tivozanib is superior to Sorafenib as measured by PFS; 2-year PFS, and ORR in this heavily-treated/relapsed or refractory population with renal cell carcinoma and is better tolerated than Sorafenib. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020